Ex Parte Fernandes et al

Patent Trials and Appeals Board

Jun 29, 2018

12062230 - (D) (P.T.A.B. Jun. 29, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/062,230 04/03/2008 Brian Fernandes
28390 7590 07/03/2018
MEDTRONIC VASCULAR, INC.
IP LEGAL DEPARTMENT
3576 UNOCAL PLACE
SANTA ROSA, CA 95403
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www .uspto.gov
ATTORNEY DOCKET NO. CONFIRMATION NO.
PA1679.0l/LG10158.L32 9913
EXAMINER
SGAGIAS, MAGDALENE K
ART UNIT PAPER NUMBER
1632
NOTIFICATION DATE DELIVERY MODE
07 /03/2018 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address( es):
rs.vasciplegal@medtronic.com
rs.patents.five@medtronic.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte BRIAN FERNANDES, JACK CHU,
and PREMA GANESAN
Appeal2017-008345
Application 12/062,230 1
Technology Center 1600
Before TONI R. SCHEINER, DEMETRA J. MILLS, and
RICHARD M. LEBOVITZ, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to an ultrasonic diagnostic
apparatus. The Examiner rejected the claims as obvious under 35 U.S.C.
§ 103. Appellants appeal the rejections pursuant to 35 U.S.C. § 134. We
have jurisdiction under 35 U.S.C. § 6(b ). The rejections are affirmed-in-part
and reversed-in-part. A new ground of rejection is set forth pursuant to
37 C.F.R. § 41.50(b).
1 The Appeal Brief ("Appeal Br.") 2 lists Medtronic, Inc. as the real-party-
in-interest.
Appeal2017-008345
Application 12/062,230
STATEMENT OF THE CASE
Claims 31-33, 39-47, and 50-57 stand rejected in the Answer by the
Examiner as follows:
1. Claims 31, 32, 39, 41--43, 45--47, 51, 56, and 57 under 35 U.S.C.
§ 103(a) as obvious in view of Raymond (Stroke, 1999, 30: 1657-1664), Zuk
2001 (Tissue Eng., 2001, 7:211-228), Wagner (Experimental Hematology,
2005, 33:1402-16), Kehat (J. Clin. Invest., 2001, 108:407--414), Hedrick
(WO 03/022988 A2; published March 20, 2003), Leonhardt (U.S. Pat. No.
5,713,917, published February 3, 1998), and Moein (U.S. Pat. No. 6,547,767
Bl, issued April 15, 2003). Ans. 2-3.
2. Claims 31 and 33 under 35 U.S.C. § 103(a) as obvious in view of
Raymond, Zuk 2001, Wagner, Kehat, Hedrick, Leonhardt, Moein, and
Liechty (Nature Medicine, 2000, 6:1282-1286). Ans. 15.
3. Claims 31 and 33 under 35 U.S.C. § 103(a) as obvious in view of
Raymond, Zuk, Wagner, Kehat, Hedrick, Leonhardt, Moein, Zuk 2002
(Molecular Biology of the Cell, 2002, 13:4279-4295), and Baum (Proc.
Natl. Acad. Sci., 1992, 89:2804--2808). Ans. 17.
4. Claims 31 and 39-44 under 35 U.S.C. § 103(a) as obvious in view
of Raymond, Zuk 2001, Wagner, Kehat, Hedrick, Leonhardt, Moein, and
Cragg (U.S. Pub. Pat. App. No. 2002/0016611 Al, published Feb. 7, 2002).
Ans. 19.
5. Claims 31 and 50 under 35 U.S.C. § 103(a) as obvious in view of
Raymond, Zuk 2001, Wagner, Kehat, Hedrick, Leonhardt, Moein, and
Simper (Circulation, 2002, 106: 1199-1204). Ans. 21.
6. Claims 31 and 52 under 35 U.S.C. § 103(a) as obvious in view of
Raymond, Zuk 2001, Wagner, Kehat, Hedrick, Leonhardt, Moein, and
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Application 12/062,230
Wobus (Embryonic Stem Cells: Methods in Molecular Biology, 2001,
185:127-156). Ans. 23.
7. Claims 31 and 52-54 under 35 U.S.C. § 103(a) as obvious in view
of Raymond, Zuk 2001, Wagner, Kehat, Hedrick, Leonhardt, Moein,
Wobus, and Drab (FASEB J, 1997, 11:905-915). Ans. 24.
8. Claims 31 and 55 under 35 U.S.C. § 103(a) as obvious in view of
Raymond, Zuk 2001, Wagner, Kehat, Hedrick, Leonhardt, Moein, W obus,
Simper, and Dennis (Stem Cells, 2002, 20:205-214). Ans. 25-26.
In the Examiner's Answer, the Examiner withdrew the rejections in
the Final Action, and set forth the new grounds of rejection listed above.
Leonhardt and Moein are newly cited in all the rejections. However, only
the basis of Rejection 1 changed to reflect the new teachings in Leonhardt
and Moein. The bases of rejections 2-8, involving the dependent claims
only, did not change. Rejections 2-8 were modified to include the newly
cited Leonhardt and Moein; however, the latter publications were not relied
upon in finding the limitations appearing in the dependent claims obvious.
There are two independent claims, claims 31 and 51. Claim 31, which
is representative, is reproduced below:
31. A method of treating an aortic aneurysm in an individual at
the aortic aneurysmal site using self-derived cells, comprising:
-harvesting adult stem cell-containing tissue from the
individual wherein said tissue is selected from the group
consisting of adipose tissue, bone marrow and peripheral blood;
-isolating adult mesenchymal stem cells from the tissue;
-culturing the isolated adult mesenchymal stem cells
under conditions where the stem cells form spontaneously
contracting vascular smooth muscle cells, wherein the
spontaneously contracting vascular smooth muscle cells express
the vascular-specific splice variant of the vascular smooth
muscle myosin heavy chain (MHC); and
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Application 12/062,230
-delivering the cells, after culturing, directly into the wall
of a blood vessel at said aortic aneurysmal site by liquid
delivery means wherein said blood vessel wall is repaired and
said aneurysm is treated in said individual.
REJECTION 1
Claim 31 is directed to a method of treating an aortic aneurysm in an
individual using "self-derived cells." The method recites the steps of
isolating mesenchymal stem cells from a tissue and delivering them into the
wall of a blood vessel. The cells are obtained from a tissue of the individual
containing adult stem cells. The tissue is adipose tissue, bone marrow, or
peripheral blood. The cells are cultured under conditions where
the stem cells form spontaneously contracting vascular smooth
muscle cells, wherein the spontaneously contracting vascular
smooth muscle cells [VSMC] express the vascular-specific
splice variant of the vascular smooth muscle myosin heavy
chain (MHC).
Claim 51 has substantially the same limitations.
The Examiner found that Raymond describes treating a carotid artery
aneurysm in a dog at the aneurysmal site using vascular smooth muscle cells
("VSMC") harvested from an artery tissue of the dog. Ans. 3--4. The
Examiner further found that Raymond describes "delivering the vascular
smooth muscle cells directly into the lateral wall aneurysm of carotid artery
to completely occlude/embolize said aneurysm." Id. at 4.
The Examiner acknowledged that Raymond does not describe
isolating mesenchymal cells from adipose tissue as one of the three possible
sources of cells recited in claim 31. Ans. 5. However, the Examiner cited
several prior art publications that the Examiner found to describe obtaining
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vascular smooth muscle cells from stem cells. These findings are
summarized below:
1) The Examiner found that Zuk 2001 teaches isolating stem cells
from adipose tissue (processed lipoaspirate or PLA) and that, after culturing
the cells,
these cells express skeletal muscle myosin heavy chain (MHC).
which is a well-known marker indicative of initiation of
differentiation toward vascular smooth muscle cells (VSMCs)
(cultured under conditions where the stem cells form VSMCs)
(see page 222, Fig. 7). Zuk [2001] isolated PLA cells that
comprise MSCs that express skeletal muscle MHC are
structurally identical as instantly claimed cells ....
Ans. 5 (boldface omitted).
2) The Examiner further cited Kehat for teaching culture conditions
for embryonic stem cells that result in muscle cells that spontaneously
contract. Ans. 6.
3) The Examiner also cited Galmiche2 as teaching that bone marrow
mesenchymal cells differentiate in culture into vascular smooth muscle-like
cells. Ans. 6.
4) The Examiner found that Hedrick teaches mesenchymal stem cells
present in lipoaspirate that "possess the capacity, for myogenic
differentiation showing the expression of the MHC, a later marker of
myogenic differentiation." Ans. 6.
The Examiner newly cited Leonhardt and Moein for teaching delivery
of cells into the blood vessel wall. Ans. 7.
2 Galmiche, Blood, 1993, 82(1):66-76. Galmiche was cited by the Examiner
for the first time in the Answer, but was not included in the statement of the
rejection.
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The Examiner concluded that one of ordinary skill in the art would
have had reason:
to substitute the Raymond VSMCs directly delivered into the
lateral wall aneurysm of carotid artery for treating the
aneurysmal site with the Zuk/Kehat VSMCs derived from PLA
MSCs differentiated into VSMCs given both Raymond and
Zuk/Kehat and Hedricks teach VSMCs and autologous nature of
stem cells, VSMCs derived from PLA MSCs together with their
multipotentiality and ease of procurement, make these cultured
MSCs an excellent choice for many tissue engineering
strategies and cell-based therapies.
Ans. 8.
The Examiner also found that Leonhardt and Moein provide the
motivation for direct delivery of cell-based therapeutic agent into the
aneurysmal site because these publications teach the benefit of delivering
therapeutic agents with a catheter into a blood vessel wall, including
delivering therapeutic cells into the tunica media of the blood vessel wall.
Id.
Discussion
Would it have been obvious to have produced the contracting vascular
smooth muscle cells as claimed?
Appellants contend that the Examiner did not identify a reason to have
"cultur[ ed] the isolated adult mesenchymal stem cells under conditions
where the stem cells form spontaneously contracting vascular smooth
muscle cells" as required by independent claims 31 and 51. Reply Br. 2-3.
While Appellants acknowledge that Kehat teaches embryoid bodies, as does
the '230 Specification, Appellants distinguish Kehat based on its teaching
that the embryoid bodies form cardiomyocytes, which are not vascular
smooth muscle cells. Appellants identify disclosure in the '230
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Specification that "the presence of selected cytokines, growth factors, and
angiogenic factors can affect the cells into which stem cells differentiate" as
evidence that the conditions in Kehat resulted in a different cell type than the
cell type which is claimed. Id. at 3.
We agree with Appellants that the Examiner erred in finding that
Kehat describes vascular smooth muscle cells. Kehat expressly discloses
forming cardiomyocytes from embryoid bodies. Kehat, Abstract. The
Examiner did not establish that cardiomyocytes are vascular smooth muscle
cells.
It is unclear why Appellants did not address the additionally cited Zuk
2001 and Hedrick publications. However, we have looked at these
publications and find each disclose the expression of MyoD 1 in cells, which
is indicative of skeletal muscle, not vascular smooth muscle cells. Zuk 2001
222 (Fig. 7); Hedrick 61; Weintraub. 3
Thus, neither Kehat, Zuk 2001, nor Hedrick describes vascular
smooth muscle cells as required by the claims.
Nonetheless, Galmiche teaches that stromal cells obtained from bone
marrow cells, when placed into culture, differentiate into vascular smooth
muscle cells. Galmiche 66 (Abstract). Stromal cells contain mesenchymal
stem cells. Zuk 2001 212 ("The bone marrow stromal, in both animals and
humans, is heterogenous [heterogeneous] in composition, containing several
cell populations, including a stem cell population termed mesenchymal stem
cells or MSCs.").
3 Weintraub, Science, 1991, 251(4995):61---66 (Abstract only).
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While Gahniche does not teach the conditions to obtain spontaneously
contracting vascular smooth cells, Drab, cited in Rejection 7, discloses such
conditions, including the addition of retinoic acid, which is the same
compound utilized in the '230 Specification to induce vascular smooth
muscle differentiation. Drab 906 ("Cell cultures"), 908 ("RESULTS"; Fig.
1); '230 Spec. ,-r 47.
Kehat teaches spontaneously contracting muscles cells and the
advantage of implanting such cells derived from stem cells into damaged
tissue. Kehat 407, 414. Thus, it would have been obvious to one of ordinary
skill in the art to have utilized the cells in Galmiche, differentiated as
described in Drab, as the source of cells for Raymond's aneurysm repair
method.
With respect to the limitation in the claims that the source of cells is
peripheral blood, the '230 Specification admits that it was known to isolate
smooth muscle cells from it. '230 Spec. i-f 41. The publication cited in the
'230 Specification for this teaching is Simper, which teaches that the
expansion of smooth muscle cell progenitor cells "may have implications for
cell, gene, and tissue engineering approaches to vascular disease" (Simper
1203-1204), providing reason to have used them in Raymond's method.
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Although Gahniche was cited in the Answer, it was not a part of the
statement of the rejection of record. Consequently, we shall designate this
rejection as new grounds under 37 C.F.R. § 41.50(b). 4 In addition, we
newly cite admissions in the Specification and Simper.
Delivery cells into the wall of a blood vessel
The Examiner newly cited Leonhardt and Moein to meet the
limitations of delivering the cells into the wall of a blood vessel, or into the
tunica media wall of a blood vessel, at an aortic aneurysm cite as recited in
claims 31 and 51, respectively.
Appellants contend that the Examiner did not provide a rational basis
to have used Leonhardt and Moein to deliver vascular smooth muscle cells
to the wall of a blood vessel to treat an aneurysm. Reply Br. 4. Appellants
contend:
4
[T]he Examiner identified no teaching in Moein to treat an
aortic aneurysmal site or to deliver a cell at an aortic
aneurysmal site.
We therefore view the reference to Raviola and Mitsui, at page
4 of the Answer [but not in the statement of the rejection], as an
improper effort to bring these references in the "back door".
Compare In re Hoch, 428 F.2d 1341, 1342 n. 3, 166 USPQ 406,
407 n. 3 (CCPA 1970) (where reference is relied on to support a
rejection, whether or not in a "minor capacity", there would
appear to be no excuse for not positively including that
reference in statement of the rejection). Ra viola and Mitsui are
not positively included in the statement of rejection, and we
have considered the issue under 3 5 USC 103 based solely on
the evidence contained in Ishikawa and Billmeyer.
Ex parte Raske, 28 USPQ2d 1304, 1305 (BPAI 1993).
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Leonhardt does not teach "treating aortic aneurysm as
claimed," as asserted by the Examiner. (Examiner's Answer,
page 15.) ... [N]othing in Leonhardt teaches using "self-
deri ved cells" or delivering cells directly into the wall of a
blood vessel.
Reply Br. 5.
We agree that Leonhardt does not describe administering cells into the
wall of a blood vessel. However, as found by the Examiner, Moein teaches
this step:
A first syringe assembly is supported by the catheter assembly
for allowing a first therapeutic substance to be injected into a
tissue of a passageway .... The needle of the first syringe
assembly can be configured to penetrate into the tunica media
layer of a blood vessel wall for administering the first
therapeutic substance to a region of the tunica media layer of
the blood vessel wall.
Moein, col. 3, 11. 26-41.
Moein teaches that the therapeutic substance can include genetically
engineered cells. Moein, col. 9, 1. 66 to col. 10, 1. 1.
As discussed in Raymond, it is not likely that the grafted vascular
cells became part of the neointima of the vessel wall, but rather it is more
likely that the vascular cells participate in the healing process by producing
extracellular matrix (ECM) materials. Raymond 1662 ("VSMC Grafts and
Vessel Wall Healing"), 1657 (first paragraph). Moein teaches delivering
therapeutic substances into the blood vessel wall, where such substances
include cells. Moein, col. 9, 1. 66 to col. 10, 1. 1. Thus, it would have been
obvious to one of ordinary skill in the art to have utilized Moein's technique
to deliver cells into the wall of an aneurysm site to facilitate introduction of
the cells into the wall of the blood vessel for delivery of therapeutic ECM to
the damaged aneurysm site.
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We reverse Rejection 1, but set forth a new ground of rejection
pursuant to 37 C.F.R. § 41.50(b) as follows:
Claims 31and51under35 U.S.C. § 103(a) as obvious in view of
Raymond, Galmiche, Drab, Moein, Zuk 2001, Kehat, Simper, and
Admissions in the '230 Specification. The teachings in Simper and the
Admissions are cited to reach the "peripheral blood" limitations of the
claims.
We leave it to the Examiner to address the obviousness of dependent
claims 32, 39, 41--43, 46, 47, 56, and 57.
REJECTIONS 2-8
Appellants did not provide arguments for rejections 2-8. We thus
affirm these rejections for the reasons set forth by the Examiner.
TIME PERIOD FOR RESPONSE
This decision contains a new ground of rejection pursuant to
37 C.F.R. § 41.50(b). Section 41.50(b) provides "[a] new ground of
rejection pursuant to this paragraph shall not be considered final for judicial
review." Section 41.50(b) also provides:
When the Board enters such a non-final decision, the appellant,
within two months from the date of the decision, must exercise
one of the following two options with respect to the new ground
of rejection to avoid termination of the appeal as to the rejected
claims:
( 1) Reopen prosecution. Submit an appropriate
amendment of the claims so rejected or new Evidence relating to
the claims so rejected, or both, and have the matter reconsidered
by the examiner, in which event the prosecution will be
remanded to the examiner. The new ground of rejection is
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Application 12/062,230
binding upon the examiner unless an amendment or new
Evidence not previously of Record is made which, in the opinion
of the examiner, overcomes the new ground of rejection
designated in the decision. Should the examiner reject the claims,
appellant may again appeal to the Board pursuant to this subpart.
(2) Request rehearing. Request that the proceeding be
reheard under §41.52 by the Board upon the same Record. The
request for rehearing must address any new ground of rejection
and state with particularity the points believed to have been
misapprehended or overlooked in entering the new ground of
rejection and also state all other grounds upon which rehearing
is sought.
Further guidance on responding to a new ground of rejection can be
found in the MPEP § 1214.01.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l). See 37 C.F.R.
§§ 41.50(±), 41.52(b).
AFFIRMED-IN-PART; REVERSED-IN-PART; 37 C.F.R. § 41.50(b)
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